This Program Project is a multidisciplinary coordinated effort aimed at preventing AIDS through development of HIV-1 vaccines. The proposal encompasses the important issues of HIV-1 strain variation and cross-immunogenicity with SIV, the production and composition of conventional and novel HIV immunogens, toxicity tests and induction of HIV-specific humoral and cellular immunity in small animals, and efficacy tests of candidate vaccines in HIV- challenged chimpanzees. Selection of candidate vaccines for efficacy tests in chimps and possible scale up for human use will, thus, be based on a systematic, scientific approach including quantitative estimation of immune response on humoral and cellular levels in guinea pigs and rhesus monkeys. The specific aims of this overall Program Project Grant Proposal are as follows: 1) To compare several HIV-1 strains, selected on the basis of clinical features, biologic properties and serotyping, for toxicity and immunogenicity in guinea pigs and rhesus macaques. 2) Based on results obtained in Aim #1, to develop candidate HIV- 1 vaccine preparations using: a) inactivated whole virus, b) genetically engineered pol mutants, c) recombinant DNA envelope and core subunits expressed in yeast and mammalian cells, and d) effective adjuvants. 3) To test the efficacy of optimum HIV-1 vaccine materials and protocols, chosen on the basis of results obtained above, for protection against HIV-1 challenge in uninfected chimpanzees. This Program Project consists of 5 participating laboratories (Projects I-V) in 4 separate institutions, a) Department of Pathology, University of California, Davis, School of Medicine (UCD)(Project I), b) Tumor Virus Laboratory, Cancer Research Institute, University of California, San Francisco (UCSF)(Project II), c) Chiron Corporation, Emeryville, CA (Project III), d) Liposome Laboratory, Cancer Research Institute (UCSF)(Project IV), and e) Southwest Foundation for Biomedical Research, San Antonio, Texas (Project V). We believe this consortium makes sense by providing the scientific talent, unique resources and administrative competence to carry out the teamwork necessary to accomplish the stated objectives.